Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy

Abstract

Autoantibodies recognising phosphorylated heat shock factor 1 (HSF1-PO4) protein are suggested as potential new diagnostic biomarkers for early-stage high-grade serous ovarian cancer (HGSOC). We predicted in silico B-cell epitopes in human and murine HSF1. Three epitope regions were synthesised as peptides. Circulating immunoglobulin A (cIgA) against the predicted peptide epitopes or HSF1-PO4 was measured using ELISA, across two small human clinical trials of HGSOC patients at diagnosis. To determine whether chemotherapy would promote changes in reactivity to either HSF1-PO4 or the HSF-1 peptide epitopes, IgA responses were further assessed in a sample of patients after a full cycle of chemotherapy. Anti-HSF1-PO4 responses correlated with antibody responses to the three selected epitope regions, regardless of phosphorylation, with substantial cross-recognition of the corresponding human and murine peptide epitope variants. Assessing reactivity to individual peptide epitopes, compared to HSF1-PO4, improved assay sensitivity. IgA responses to HSF1-PO4 further increased significantly post treatment, indicating that HSF1-PO4 is a target for immunity in response to chemotherapy. Although performed in a small cohort, these results offer potential insights into the interplay between autoimmunity and ovarian cancer and offer new peptide biomarkers for early-stage HGSOC diagnosis, to monitor responses to chemotherapy, and widely for pre-clinical HGSOC research.